The pivotal LUM001-304 (ICONIC) trial was an open-label, phase IIb study conducted to evaluate the safety and efficacy of maralixibat in children with Alagille Syndrome (ALGS) between the ages of 1 and 18 years. A total of 31 patients enrolled into the study, which was conducted at 10 clinical sites in Australia, Europe, and the UK. The study comprised an 18-week open-label run-in period, a 4-week randomized, double-blind, placebo-controlled drug-withdrawal phase, followed by a 26-week stable-dosing period, and an optional long-term treatment period.
Efficacy outcomes included changes in sBA, pruritus assessed using the Itch Reported Outcome (ItchRO) tools, liver biomarkers and enzymes, body height and weight z scores, and health-related quality of life (HRQoL) as measured by the Pediatric Quality of Life Inventory (PedsQL). The study found a significant reduction in sBA levels and improvements in pruritus severity in patients treated with maralixibat compared to placebo. Additionally, there were improvements in HRQoL measures, although the study noted the need for further research to confirm these findings due to the small sample size and the exploratory nature of the trial.
Harms outcomes were also assessed, with the incidence of adverse events (AEs) being similar across treatment phases. The most frequently reported AEs included abdominal pain, pyrexia, diarrhea, nasopharyngitis, vomiting, cough, and pruritus. Serious adverse events (SAEs) were reported in a small number of patients, but none were considered related to the study medication.
The clinical experts consulted for the review highlighted the unmet need for effective treatments for cholestatic pruritus in ALGS patients, noting that current off-label treatments are often ineffective. Maralixibat represents a potential new treatment option for these patients, with the trial results suggesting it could be used in combination with current therapies or as an initial treatment for new patients presenting with severe pruritus.
Despite the promising results, the study's limitations, including its small sample size and the lack of long-term efficacy and safety data, underscore the need for further research. The clinical experts also noted the challenges of conducting controlled clinical trials in this patient population, particularly for patients younger than 12 months. Nonetheless, the trial results provide valuable insights into the potential benefits of maralixibat for treating cholestatic pruritus in ALGS patients, offering hope for improved management of this challenging condition.
